This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. The great body of evidence developed over the last 10-20 years suggests that type 1 diabetes in humans is a chronic, slowly progressive autoimmune disease. The objective of this study is to identify immune intervention strategies that will prevent the progression of beta cell destruction from the time of onset of type 1 diabetes. The persistence of at least some beta cells should improve long-term diabetes care and prevent not only complications of the disease itself but also hypoglycemia, which is a consequence of its management. The aim is to arrest beta cell destruction in newly diabetic subjects because immune modulation may not work well alone once the autoimmune process has progressed so far as to result in overt disease. The study's rationale is to demonstrate a meaningful preservation of islet function with minimal immune system effects over the 4-year course of this study. The data from this clinical trial could serve as the basis for a larger trial if the results are sufficiently positive, or they could suggest other combined interventiontrials that might achieve either better efficacy or potentially preserve C-peptide without the need for continued immunosuppression. The complications of long-term diabetes are well known, and the costs of caring for diabetes and its complications are currently greater than 0 billion a year. The DCCT and other studies have demonstrated that improved metabolic control can reduce the long-term complications of diabetes [6]. Thus, an intervention, which could restore normal islet function and maintain production of insulin would significantly improve the prognosis for metabolic control of diabetes and thus reduce long-term complications.